Principle objectives of this research are to obtain detailed information about the molecular structure of pituitary growth hormone, prolactin, and related proteins, and to determine relationships between structure and biological activity. The starting point for these studies is the sequence analysis of bovine growth hormone, currently being completed, and of sheep growth hormone and bovine prolactin, now in progress in this laboratory. Sequence analysis of growth hormones and prolactins from additional animal species is also proposed. Data on these primary structures will be used to examine homologies and evolutionary relationships among growth hormones and prolactins and to search for potenial homologies with other hormonal proteins. In collaborative studies, the biological activity of fragments of growth hormone and prolactin produced with cyanogen bromide and other specific cleavage reagents will continue to be evaluated in an attempt to define the area or areas of these molecules which are responsible for binding to target cells or constitute active sites or centers. Additional segments of the hormones will be produced synthetically by solid phase methodology to refine data obtained from natural fragments and to study the effects of specific amino acid substitutions on molecular properties and activity. Both synthetic and natural fragments will also be used to investigate the nature and location of antigenic sites in the hormones. Studies on the specific chemical modification of reactive amino acid side chains in the native hormone will be continued in order to evaluate the effects of limited molecular perturbations on activity and antigenicity. Use will be made of growth hormone and prolactin covalently linked to Sepharose or other insoluble supports to isolate specific antibodies for immunochemical studies and also as a tool for exploring the interaction of these proteins with small molecules and macromolecular components of cell membranes.